Date: Sunday, October 21, 2018
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Rheumatoid Arthritis (RA) is a disease characterized by chronic inflammation of the synovial tissue in joints. It is driven by highly activated B cells. Synovial cells, primarily Fibroblast like synoviocytes (FLS) play an important role in activating these B cells. It was previously shown, that FLS upregulate CD40L under pro-inflammatory conditions (other abstract). In order to investigate the interactions responsible for B cell activation, a co-culture model was established with RAFLS and SF from Osteoarthritis (OA) patients.
IgD+ B cells were isolated from human peripheral blood by MACS and co-cultured w/wo SFs in medium only, in the presence of CpG, IFN-gamma, TNF-alpha or both, respectively. B cell subpopulations, survival and proliferation were determined by FACS. IgG and IgM were measured by ELISA. Images of co-cultures were produced by immunocytochemistry.
B cell survival is increased in co-culture after 6 days without additional stimulation (RAFLS: +20.65% +/-1.27%; OAFLS: +14.53 % +/- 5.54 % compared to B cell control) Proliferation of B cells is already increased after 3 hours of co-culture without additional stimulation (RASF: +13.48 % +/- 2.16 %; OASF: +13.02 % +/- 1.16 % compared to B cell control). Without additional stimulation IgD+ B cells are reduced in FLS co-culture after 6 days (RAFLS: -26.2 % +/- 12.8 %; OAFLS: -23.1 +/- 5.5 % compared to B cell control). With IFN-gamma, the reduction of IgD+ B cells is even more pronounced (RAFLS: -44.6 % +/- 4.7 %; OAFLS: -33.6 % +/- 9.2 % compared to B cell control). The proportion of CD138+ B cells is increased after 6 days in co-culture (RAFLS: from 0.37 % to 14.8 % +/- 0.9 %; OAFLS: from 0.37 % to 15 % +/- 2.9 %) IgM could only be measured in considerable amounts in the supernatant after stimulation with CpG and exclusively in the co-cultures (RAFLS: from: 6.7 ng/mL +/- 0.95 ng/mL to 517.5 ng/mL +/- 228.4 ng/mL; OAFLS: from: 5.9 ng/mL +/- 0.3 ng/mL to 189.6 ng/ml +/-204.4 ng/ml) IgG could not be detected in the supernatant above baseline levels. However, immunofluorescence staining showed IgG positive B cells in the co-cultures.
FLS are capable of inducing CSR in naïve B cells, probably through CD40L upregulated under pro-inflammatory conditions (shown in other abstract), but they do not supply enough stimulation to drive the B cells to immunoglobulin secretion. TLR stimuli (or hypothetically BCR stimuli) are required for Ig release.
To cite this abstract in AMA style:Bleck D, Lowin T, Schneider M, Pongratz G. Fibroblast like Synoviocytes (FLS) Are Capable of Inducing Phenotypical Changes Including Class Switch Recombination (CSR) in Naive B Cells, but Additional Factors Are Required to Trigger Immunoglobulin Secretion [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/fibroblast-like-synoviocytes-fls-are-capable-of-inducing-phenotypical-changes-including-class-switch-recombination-csr-in-naive-b-cells-but-additional-factors-are-required-to-trigger-immunoglobul/. Accessed September 21, 2019.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/fibroblast-like-synoviocytes-fls-are-capable-of-inducing-phenotypical-changes-including-class-switch-recombination-csr-in-naive-b-cells-but-additional-factors-are-required-to-trigger-immunoglobul/